(1) Field of the Invention
The present invention relates to processes for the preparation of 1,4,7,10,13,16,21,24-OCTAAZABICYCLO[8.8.8]HEXACOSANE (H6Aza222) (1) and 1,4,7,10,13,16,21,24-OCTAAZABICYCLO[8.8.8]HEXACOSA, 4,6,13,15,21,23-HEXAENE (2). In a preferred process, the present invention relates to the preparation of compound (2) by reacting tris(2-aminoethyl) amine (tren), isopropyl alcohol (i-PrOH), and triethylamine (Et3N) with cooling at a temperature below −30° C. Further, the present invention relates to the preparation of compound 1 from compound 2 by reacting an alkali metal and ammonia with compound 2 with cooling to a temperature below −30° C.
(2) Description of Related Art
Aza containing cryptands are known in the art and have a variety of uses as noted in U.S. Pat. No. 4,888,032 for instance. Such uses include, for instance, medical uses, water purification removing toxic heavy metals, binding metals as catalysts, electrides and alkalides. They are analogous to the non-aza cryptands of U.S. Pat. No. 4,257,955 to Gansow et al and U.S. Pat. No. 5,492,879 to Dye.
There is interest in nitrogen-donor cryptands for the preparation of room-temperature stable alkalides and electrides (Kim, J., et al., J. Am. Chem. Soc., 121 10666-10667 (1999)) which led to reinvestigation of the synthesis of 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1), the aza analog of cryptand [2.2.2] (Xie, Q., et al., J. Am. Chem. Soc. 122 6971-6978 (2000)). Compound 1 was used for the preparation of the first barium sodide (Redko, M. Y., et al., JACS 125 2259-2263 (2003)). A reaction sequence in which tren is condensed with glyoxal to form the intermediate 1,4,7,10,13,16,21,24-octaazabicyclo [8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) has been described by Smith et al (Smith, P. H., et al., J. Org. Chem. 58 7939-7941 (1993)), who also obtained the crystal structures of both compounds 1 and 2. While this method is satisfactory, it leads to gelatinous byproducts which lowered the yield and required the separation of compound 2 from the gelatinous byproducts via a 3-day Soxhlet extraction followed by filtration. The gels are polymers formed from the reactants and are very difficult to separate from the compound 2. The purified compound 2 was then reduced with LiAlH4 in THF or NaBH4 in MeOH to give a low overall purified yield of 45% of compound 1. A large excess of moderately expensive reducing agent(s) is required.